Hair and Hair Follicles
Visual terminal hair extends above the surface of the skin. Hair is a fully cornified structure that results from complete maturation of follicular matrical cells emanating from the hair follicle (HF).
Hair is not a biologically active structure. However, the HF, and, in particular, the matrix cells of the HF bulb, have high metabolic activity. Matrix cells of human scalp HFs and bone marrow cells have the most active replicating time of any normal tissue.
The scalp HF extends from the epidermis to the bulb situated in the subcutaneous fat. Histologically, the HF may be divided into the upper segment and lower segment. The upper segment is composed of an infundibulum part and isthmus part that extends to the site of the muscle erection. The lower segment extends from the point of attachment of the muscle of erection to the base. The lower segment consists of the stem and bulb.
Indeed, each HF can be considered an independent highly specialized organelle composed of many cell types, such as melanocytes, epidermal and mesenchymal cells. Cells in the HF are in all stages of growth and differentiation during the active anagen (growth) cycle. In addition, each cell type renders different function(s) for the development of the terminal hair. The follicular germ cells, which are the bulbar matrix cells, are responsible for the great mitotic proliferation in the HF.
During development, the cells in the matrix proliferate with an upward migration and differentiation into hair matrix, inner sheath and outer sheath cells. The hair matrix group, located in the central axis of the HF, further differentiates into the cells forming the medulla, hair cortex, and hair cuticle. These cells show a continuous upward migration with keratinization of the cortical and cuticle cells which are essential for the manufacturing process of hair in a growing follicle. (Chase HB, Physiol. Rev. 1954; 34: 113-126, Hashimoto K, Br. J. Dermatol 1970; 83: 167-176. DeVillez RL:In: Current Concept, A Scope Publication, by the Upjohn Co., Kalamazoo, Mich., 1986; pp. 4-27; Takashima I, Kawagihi, I: In: Toda K, et al (eds): Biology and Disease of Hair. Baltimore, Univ. Park Press, 1976; pp. 457-471. Jakubovic H R, Ackerman A B In: Moschella S L, Hurley H J, eds: Dermatology. W. B. Saunders Co., 1992, pp. 3-87).
Oxidative stress produced from environmental chemical and physical agents as well as oxidants produced as by-products of cellular metabolism are extremely toxic to cells. Actively proliferating cells are highly susceptible to oxidant damage. Indeed, oxygen radical stress induced by environmental and/or as a result of endogenous metabolism can be overwhelming and lead to DNA damage. (Poot M, Mutation Res 1991; 256: 177-189).
The effect of oxidative stress and antioxidants on HF has not been previously elucidated. In the present invention, it is postulated that the HF, being an actively proliferating organelle, is highly susceptible to damage by environmental and/or endogenous oxidants.
It is an object of the present invention to provide protective formulations for the protection of HFs against oxidative stress.
It is a further object of the present invention to provide formulations which can be administered to a subject and which provide protection of HFs against damage by environmental and/or endogenous oxidants.